高通量虚拟筛选CDK2/Cyclin A2靶点抑制剂

CDK2/Cyclin A2复合蛋白的异常表达与乳腺癌、 口腔癌、 食管鳞状细胞癌的发生密切相关. CDK2/ Cyclin A2复合蛋白的活性位点不同于CDK2单体. 至今临床上尚无靶向此复合蛋白的药物分子. 针对CDK2/Cyclin A2复合蛋白, 以实验报道的10个抑制剂分子构建药效团模型, 通过药物体外药代动力学（ADME）、 Docking、 聚类分析、 毒性预测, 从DrugBank, ChEMBL和TCM@Taiwan 3个数据库约90万组数据中进行高通量虚拟筛选, 进一步进行MD模拟、 MM/PBSA结合自由能计算、 能量分解和平均非共价作用(aNCI)分析, 筛选出3个抑制效果优于阳性实验药Roscovitine的先导分子: DrugBank-2004, DrugBank-583和ChEMBL-7122. 与CDK2蛋白相比, CDK2/Cyclin A2复合蛋白结合位点空间变大, 先导分子与Lys33, Asp86, Lys129和Asp145残基之间的排斥作用有所降低, 导致结合自由能更大.     

以四乙基氢氧化铵为模板并通过转晶法合成高硅铝比的SSZ⁃13沸石分子筛

使用四乙基氢氧化铵为有机模板剂,以低硅铝比(nSiO2/nAl2O3)的Y分子筛为铝源,通过转晶法制备结晶度良好的SSZ?13沸石分子筛。从凝胶配比方面考察了不同原料组成对分子筛合成的影响,并通过X射线衍射(XRD)、扫描电子显微镜(SEM)及电感耦合等离子体(ICP)表征水热反应过程中的物相、形貌、硅铝比等变化,揭示分子筛合成过程。氨选择性催化还原(NH3?SCR)反应显示该分子筛具有优异的催化活性,为其工业上的广泛应用提供了可能性。     

Synthesis and antibacterial activity of ethyl 2-amino-6-methyl-5-oxo- 4-aryl-5,6-dihydro-4H-pyrano[3,2-c]quinoline-3-carboxylate

The three-component reaction of 4-hydroxy-1-methyl-2(1H)-quinolinone, aromatic aldehydes and ethyl cyanoacetate was carried out in the presence of a catalytic amount of 4-dimethyl aminopyridine(DMAP) in aqueous ethanol. The reactions result in the formation of pyranoquinoline derivatives in excellent yields. Antibacterial activity has been evaluated against Gram positive and Gram negative bacteria for some of the synthesized compounds. The results indicated that these compounds are moderately effective against bacterial growth and their effectiveness is highest against Pseudomonas aeruginosa.     

Electrochemical sensor based on f-SWCNT and carboxylic group functionalized PEDOT for the sensitive determination of bisphenol A

A simple,sensitive,and reliable method for the voltammetric determination of bisphenol A(BPA) by using carboxylic group functionalized single-walled carbon nanotubes(f-SWCNT)/carboxylic-functionalized poly(3,4-ethylenedioxythiophene)(PC4) complex modified glassy carbon electrode(GCE) has been successfully developed.The electrochemical behavior of BPA at the surface of the modified electrode is investigated by electrochemical techniques.The cyclic voltammetry results show that the as-prepared electrode exhibits strong catalytic activity toward the oxidation of BPA with a well-defined anodic peak at 0.623 V in PBS(0.1 mol/L,pH 7.0).The surface morphology of the 3D network of composite film is beneficial for the adsorption of analytes.Under the optimized conditions,the oxidation peak current is proportional to BPA concentration in the range between 0.099 and 5.794 μmol/L(R~2 = 0.9989),with a limit of detection of 0.032 μmol/L(S/N = 3).The enhanced performance of the sensor can be attributed to the excellent electrocatalytic property of/-SWCNT and the extraordinary conductivity of PC4.Furthermore,the proposed modified electrode displays high stability and good reproducibility.The good result on the voltammetric determination of BPA also indicates that the asfabricated modified electrode will be a good candidate for the electrochemical determination and analysis of BPA.     

Allyl phthalazinone synthesis,polymerization and polymer properties

A phthalazinone monomer with an allyl group, i.e. 4-（3-allyl-4-hydroxyphenyl）phthalazin-1（2H）-one, was synthesized and then copolymerized with 4-（4-hydroxylphenyl）（2H）-phthalazin-1-one and 2,6- diflurobenzonitrile by means of aromatic nucleophilic polycondensation to provide a series of crosslinkable poly（aryl ether nitrile）s. The virgin copolymers exhibited good solubility in polar organic solvents with relative high molecular weights （Mw： 45,130-58,403, inherent viscosities： 0.58-0.75 dL/ g）. After cross-linking, the thermal stability and solvent resistance of the polymer increased.     

Nickel-catalyzed cross-coupling reaction of alkynyl bromides with Grignard reagents

We describe a convenient method for the synthesis of 1,2-disubstituted acetylenes via a cross-coupling reaction of （bromoethynyl）benzene with Grignard reagents. The reaction of （bromoethynyl）benzene （1 mmol） with Grignard reagent （1.3 mmol） mediated by NiCl2 （4 mol%） and （p-CH3Ph）3P （8 mol%） in THF could produce 1,2-disubstituted acetylenes in good yields at room temperature.     

Chemoselective hydrogenolysis of tetrahydrofurfuryl alcohol to 1,5-pentanediol over Ir-MoOx/Si02 catalyst

In this work, MoOx promoted Ir/SiO2 catalysts were prepared and used for the selective hydrogenolysis of tetrahydrofurfuryl alcohol （THFA） to 1,5-pentanediol in a continuous flow reactor. The effects of different noble metals （Ir, Pt, Pd, Ru, Rh）, supports and Ir contents were screened. Among the investigated catalysts, 4 wt%Ir-MoOx/SiO2 with a Mo/Ir atomic ratio of 0.13 exhibited the best catalytic performance. The synergy between Ix particles and the partially reduced isolated MoOx species attached on them is essential for the excellent catalytic performance of Ix-MoOx/SiO2. The catalyst exhibited a better hydrogenolysis efficiency of THFA with the selectivity of 1,5-pentanediol of 65%-74% at a conversion of THFA of 70%-75% when the initial THFA concentration is ranging from 20 wt% and 40 wt%. And higher system pressure was also in favor of the conversion of THFA. During a stability test, the conversion of THFA and 1,5-pentanediol yield over Ix-MoOz/SiO2 decreased with reaction time, which can be explained by the leaching of Mo species during the reaction.     

Effect of the graphitic degree of carbon supports on the catalytic performance of ammonia synthesis over Ba-Ru-K/HSGC catalyst

A series of high surface area graphitic carbon materials （HSGCs） were prepared by ball-milling method. Effect of the graphitic degree of HSGCs on the catalytic performance of Ba-Ru-K/HSGC-x （x is the ball-milling time in hour） catalysts was studied using ammonia synthesis as a probe reaction. The graphitic degree and pore structure of HSGC-x supports could be successfully tuned via the variation of ball-milling time. Ru nanoparticles of different Ba-Ru-K/HSGC-x catalysts are homogeneously distributed on the supports with the particle sizes ranging from 1.6 to 2.0 nm. The graphitic degree of the support is closely related to its facile electron transfer capability and so plays an important role in improving the intrinsic catalytic performance of Ba-Ru-K/HSGC-x catalyst.     

A New Terbium（III） Coordination Compound with 2-Thiophenecarboxylic Ligand： Synthesis and Crystal Structure①

A new coordination compound with formula [Tb（2-TC）3（DMF）]n （1, 2-TC = 2-thio- phenecarboxylic ligand and DMF = dimethylformamide） was synthesized by solvothermal method. The structure of compound 1 was determined by single-crystal X-ray diffraction analyses, and characterized by elemental analyses, IR and powder X-ray diffraction. Structure analysis reveals compound 1, exhibiting a one-dimensional chain structure, crystallizes in triclinic space group P21/c, with a = 9.2751（19）, b = 16.490（3）, c = 15.865（5） A, β = 118.98（2）°, V= 2122.7（9）A3, D,. = 1.916 g/cm3, Mr= 612.45 （C18H15NO7S3Tb）, F（000） = 1196,μ（MoKa） = 3.67 mm-1, Z = 4, R = 0.0616 and wR = 0.0962 for 3865 observed reflections （I 〉 2o（I））, and R = 0.1092 for all data. Meanwhile, the photoluminescent properties of compound 1 were also investigated in the solid state at room temperature.